Acute ET in a 42 yo male with recent diarrhoea OMC Fumtiaka Nonaka

17/10/2011 ED (2wk from onset) 42yo Male c/o binocular diplopia (mainly horizontal, with vertical and torsional component) difficulty in focusing, pain behind the eyes for 2/52 3-4/52 ago had acute gastroenteritis, pins and needles, unbalanced denies: ataxia, inco-ordination, other motor/sensory symptoms POH: red-green color blindness PMH: nil, no head trauma

On Examination in ED VA: R 6/5-3, L 6/9+3 Ishihara 2/15, R+L no RAPD CT: Alternating ET (PCT: not performed) EOM: LLR-, RIO+, LSR-, end point nystagmus, normal saccades, pain on looking up, no INO Bloods: FBE, U+E normal, CRP<1, RF –ve, TSH WNL, ANA detected (titre 1:80, <1:80 = negative) MRI brain (25/10/11): normal, no evidence for intracranial demyelination

What’s next?

Anti-ganglioside antibodies

04/11/11 OMC (5wk from onset) VA: R 6/5 L 6/6 HVF: W.N.L. EOM: RLR-, LLR- (see Hess) PCT: Near 35ΔET’ LH’6Δ Distance 50ΔET LH6Δ Bloods: – GQ1b IgG Ab +ve – MAG IgM IFA –ve – GM1 IgG Ab –ve, GM1 IgM Ab –ve – AChR Ab –ve

S: still diplopia to sides, after midday PCT: Near 6ΔET’ LH’3Δ Distance 6ΔET LH2Δ (see Hess) 18/11/11 OMC (7wk) Much better, SV in am, gradually develops diplopia as day progresses EOM RLR-, LLR- (see Hess) PCT: Near 14ΔET’ LH’3Δ Distance 25ΔET LH3Δ Saccades fast and accurate, no fatigue 02/12/11 OMC (9wk)

04/11/11 (5wk)18/11/11 (7wk) 02/12/11 (9wk) Distance 50 Δ ET LH6 Δ Distance 25 Δ ET LH3 Δ Distance 6 Δ ET LH2 Δ

Miller-Fisher syndrome  a variant of Guillain-Barre syndrome  a triad of ophthalmoplegia, ataxia, and areflexia  full triad of MFS is not always present  anti-GQ1b ganglioside antibodies +ve in 90% of MFS  Campylobacter jejuni, cytomegalovirus, Epstein- Barr virus, and Streptococcus pyogenes have been reported as antecedent infectious agents in MFS. (J Neurol Sci 1998;160:64–6)  good recovery with or without treatment ´ Charles Miller Fisher MD

 Acute conditions Miller-Fisher Syndrome Acute ophthalmoparesis (ophthalmoplegia without ataxia)  Chronic conditions Otherwise unexplained ophthalmoplegia Anti-GQ1b antibody Anti-Gq1b Immunolocalization of GQ1b and Related Gangliosides in Human Extraocular Neuromuscular Junctions and Muscle Spindles. F. Pedrosa-Domellof et al, IOVS 2009;50:3226 –3232 Abundant staining anti-GQ1b Abs: NMJs of human EOMs > limb muscles Absence of a blood-nerve barrierHigh capillary supply NMJs of EOMs may be easily targeted by anti-GQ1b Abs *NMJ = Neuromuscular junction *

Anti-ganglioside antibodies & diplopia “ANTI GM1 ANTIBODIES – THE CAUSE OF OTHERWISE UNEXPLAINED OPHTHALMOLPLEGIAS?” L Kowal et al, 2003 – Four patients with otherwise unexplained ophthalmoplegia – No other neurological problems – Elevated levels of IgM GM1 Ab – Normal anti-GQ1b Ab Anti-GQ1b IgG antibody syndrome: clinical and immunological range. K Hirata, et al, J Neurol Neurosurg Psychiatry 2001;70:50–55 – 194 patients with anti-GQ1b IgG – 94% had antecedent illnesses 84% upper respiratory tract infection 10% diarrhoea – As initial symptoms 67% diplopia 29% gait disturbance

The case described might be labelled “ophthalmoparesis due to presumed microvascular causes” or “presumed breakdown of latent squint” as no other explainable causes have been found. Measurement of anti-ganglioside antibodies should be considered in cases of otherwise unexplained ophthalmoplegia.